Connecting Genes, Brain & Behaviour Flashcards

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1
Q

What two things in animals are positively correlated?

A

Neural complexity and length of life.

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2
Q

What aren’t feasible with techniques that rely on breeding multiple generations?

A

Using more complex species as their lifespans are too long for multiple generations.

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3
Q

What are the four steps of forward genetics in animal models?

A

Mutagenesis, crossing, phenotype, genotype.

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4
Q

What happens in mutagenesis?

A

Inducing mutations, typically use radiation to induce mutations.

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5
Q

What happens in crossing?

A

Cross the mutated animal with one of wild-type strain, over generations some offspring will display some mutations and some will display others or not at all.

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6
Q

What happens in phenotype?

A

Identifying the phenotypes of the offspring.

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7
Q

What happens in genotype?

A

Finding the associated genotype to the phenotype

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8
Q

What do they look at in forward genetics?

A

Anatomy, learning and social behaviour

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9
Q

What happens in a reverse genetics approach?

A

Targeted mutations are introduced and the effect on the phenotype is measured

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10
Q

What is the CRISPR-Cas9 system?

A

A natural part of a bacterium’s defence against invading viruses

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11
Q

What can the CRISPR-Cas9 be used to do?

A

Can be used to create targeted genetic mutations in model organisms

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12
Q

What is Cas9?

A

A nuclease protein (an enzyme that cleaves the chains of nucleotides in nucleic acids into smaller units).

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13
Q

What does guide RNA do to the Cas9 protein?

A

Guide RNA directs the Cas9 protein to the desired DNA sequence, where the Cas9 cuts the DNA

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14
Q

What can the random repair process do to the gene?

A

Can disable the gene, or targeted sequences can be introduced to be inserted during repair

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15
Q

What is optogenetics?

A

Uses microbial opsins to excite or inhibit neurons by light

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16
Q

How do neurons respond to light?

A

Each responds to light of particular wavelengths

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17
Q

What is the adeno-associated virus (AAV) commonly used to?

A

Commonly used to introduce the required genetic material, a cell-specific promotor sequence can restrict opsin expression to particular types

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18
Q

What does the channelrhodopsin-2 (ChR2) pump respond to?

A

Responds to blue light, and allows positive ions into the cell

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19
Q

What does the channelrhodopsin-2 (ChR2) pump response result in?

A

Depolarisation results in neural excitation

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20
Q

What does halorhodopsin (NpHR) pump respond to?

A

Responds to yellow light and allows negative ions into the cell

21
Q

What does the halorhodopsin (NpHR) pump response result in?

A

Hyperpolarisation results in neuronal inhibition

22
Q

What is light stimulation delivered through?

A

Light stimulating a particular rhodopsin is delivered though an implanted optic fibre

23
Q

What does stimulating ChR2 in mouse amygdala cells do?

A

Induces a predatory response

24
Q

What does an optogenetic system in combination with a CRISPR-Cas9 system allow?

A

Light-controlled protein transcription and light controlled genome editing

25
Q

What can genetic associations with behaviour do?

A

Can only hint at the biological pathways involved

26
Q

What can we do using bioinformatives?

A

We can ‘translate’ a human genetic mutation to target a homologous gene in a model organism

27
Q

What do model organisms allow?

A

More direct measurement at multiple levels; structure, function, behaviour

28
Q

What is the HTR1A?

A

It is the human gene encoding the serotonin-1A receptor

29
Q

What can imaging genetics do?

A

Connects genes, brain anatomy, brain function and behaviour

30
Q

Where is the SNPrs6295 located?

A

In the promotor region of HTR1A

31
Q

What is the SNPrs6295 associated with?

A

Trait anxiety

32
Q

How is the SNPrs6295 associated with trait anxiety?

A

Individuals with one or two copies of the G allele showed lower trait anxiety than individuals homozygous for the C allele

33
Q

What is the SNPrs6295 also associated with?

A

Serotonin-binding potential

34
Q

How is the SNPrs6295 associated with serotonin-binding potential?

A

Additional copies of the G allele were associated with increased binding potential

35
Q

What does the G allele do?

A

Impairs the transcriptional repression of the promotor, causes increased expression of the 5-HT1A receptor

36
Q

How was binding potential measured with PET?

A

Detects radiation from an injected tracer with a high affinity for 5-HT1A receptors

37
Q

What did binding potential measured with PET find?

A

Higher density of receptors leads to higher binding potential

38
Q

What is the 5-HT1A receptor?

A

It is an autoreceptor

39
Q

Why is 5-HT1A an autoreceptor?

A

It is located at the presynaptic membrane, where it binds neurotransmitters released by the neuron. This is a key part of the system for regulating neurotransmitter release

40
Q

What is reduced capacity for regulation of 5-HT associated with?

A

Increased amygdala reactivity

41
Q

What was capacity for regulation of 5-HT release the same as?

A

Same as the PET measure of 5-HT1A binding potential

42
Q

What is increased amygdala reactivity associated with?

A

Increased trait anxiety

43
Q

What does lower levels of the SNPrs6295 G allele lead to?

A

Low 5-HT binding potential, high amygdala reactivity, high trait anxiety

44
Q

What does higher levels of the SNPrs6295 G allele lead to?

A

High 5-HT binding potential, low amygdala reactivity, low trait anxiety

45
Q

What is the HTR1A SNP associated with?

A

Amygdala reactivity, additional copies of the G allele were associated with decreased reactivity

46
Q

What is increased serotonin-binding potential throughout the brain associated with?

A

Lower anxiety

47
Q

What is this convergent evidence of?

A

Presence of the G allele of rs6295 impairs repression of HTR1A transcription, leads to increased receptor density, indexed by binding potential, in turn leads to decreased amygdala reactivity, finally predisposes to low anxiety

48
Q

What happens conversely?

A

Absence of the G allele of rs6295 promotes repression of HTR1A transcription, leads to decreased receptor density, indexed by binding potential, leads to increased amygdala reactivity, predisposes to high anxiety

49
Q

By comparing measurements across multiple levels what can we reveal?

A

The likely biological pathway linking a genetic variant to a behavioural phenotype